Aerobic Oxidative C–H Azolation of Indoles and One-Pot Synthesis of Azolyl Thioindoles by Flavin–Iodine-Coupled Organocatalysis

Abstract

The aerobic oxidative cross-coupling of indoles with azoles driven by flavin-iodine-coupled organocatalysis has been developed for the green synthesis of 2-(azol-1-yl)indoles. The coupled organocatalytic system enabled the one-pot threecomponent synthesis of 2-azolyl-3-thioindoles from indoles, azoles, and thiols in an atom-economical manner by utilizing molecular oxygen as the only sacrificial reagent.

Sulfenylation of Indoles Mediated by Iodine and Its Compounds

“…The aerobic reaction of thiols with indoles in MeCN at room temperature [24] and indolines in DMSO at 60 °C [25] delivered 3‐sulfenyl indoles in 65–94 % and 60–92 % yields respectively. Flavin‐iodine‐coupled organocatalysis also enabled the one‐pot three‐component atom‐efficient synthesis of 2‐azolyl‐3‐thioindoles from indoles, azoles, and thiols applying molecular oxygen as the terminal oxidant [26] . Flavin catalyst in these processes regenerated molecular iodine from iodide‐anion, as well as converted thiols into disulfides.…”

Electro-Oxidative C–N Bond Formation through Azolation of Indole Derivatives: An Access to 3-Substituent-2-(Azol-1-yl)indoles

“…Traditionally, the (azol-1-yl) indoles are constructed via an azole nucleophilic displacement of halogenated electro-deficient indole derivatives . The direct C–N bond formation between nonactivated indoles and azoles were usually assisted by employment of a stoichiometric amount of N -chlorosuccinimide, iodine, hypervalent iodine reagents, , or catalytical iodine/tetrabutylammonium iodine and a stoichiometric amount of chemical oxidant (Figure a). − A photocatalytic aerobic C–H azolation of indoles under mild conditions was disclosed by Nicewicz and co-workers, while the reaction efficiency of this coupling transformation is pretty low (yield around 10%) (Figure b) . Thus, the development of more efficient and environmentally friendly protocols without using expensive catalyst or excess external oxidants are still highly anticipated.…”

Metal-Free Atom-Economical Synthesis of Tetra-Substituted Imidazoles via Flavin-Iodine Catalyzed Aerobic Cross-Dehydrogenative Coupling of Amidines and Chalcones

“…Recently, we have developed a novel dual catalytic system for aerobic CDC using a coupled redox catalyst system consisting of a biomimetic flavin organocatalyst and an iodine catalyst . The coupled flavin-iodine catalyst promoted aerobic CDC through direct C–H bond functionalization when applied to the azolation of indoles, specifically the formation of imidazo­[1,2- a ]­pyridine from acetophenones and 2-aminopyridines . Although aerobic CDC generally requires transition metal catalysts, these flavin-iodine-catalyzed CDC reactions are unique metal-free systems, which facilitate non-metal redox catalysis for O 2 - and substrate activation.…”